AAAAI: Novel Phosphodiesterase Inhibitor May Find Role in COPD

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Explain to interested patients that this study involves a drug that is in preclinical investigation and is not available to the public.

Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.

NEW ORLEANS -- Preclinical experiments indicate that a new phosphodiesterase 4 inhibitor may have potent effects on chronic obstructive pulmonary disease (COPD), Indian researchers reported here.

"Our results suggest that OCID 2987 is a selective phosphodiesterase 4 inhibitor with good safety window and represents a novel inhibitor to treat COPD and asthma," said Shridhar Narayanan, PharmD, senior vice president-biology at Orchid Research Laboratories in Chennai.

In his poster presentation at the annual meeting of the American Academy of Allergy, Asthma & Immunology, Narayanan said that OCID 2987 is currently in regulatory toxicology studies.

Phosphodiesterase 4 is a major cyclic adenosine-monophosphate-metabolizing enzyme that inhibits immune and inflammatory cells, airway smooth muscle, and pulmonary nerves.

These inhibitors have shown effectiveness in animal models of COPD and asthma. Adverse events with this class of drugs appear to be mainly nausea and vomiting.

The Orchid research team evaluated OCID 2987 in a series of invitro and exvivo assays for COPD and asthma, performing pharmacokinetic studies across species.

The compound was tested in animal models in lipopolysaccharide-induced endotoxemia and neutrophilia; cigarette smoke-induced COPD; ovalbumin-induced asthma in guinea pig; and BALB/c mice; and for its emetic potential in ferret.

Narayanan said that the researchers observed that OCID 2987 inhibited phosphodiesterase4B2 enzyme at half maximal inhibitory concentration (IC50) value of 8.23 nanomoles and exhibited greater than a 1,000-fold selectivity over other phosphodiesterase isoforms.

In addition, OCID 2987:

Showed potent inhibition of various cytokines in in vitro assays

Exhibited oral bioavailability greater than 25% across species

Exhibited strong anti-inflammatory action in animal models of COPD and asthma with a wide safety margin for emesis